Dolichol is an essential isoprene lipid which is involved in the assembly of at least one major class of glycoproteins. We will assess whether or not the regulatory inter-relationship shown by us to exist between rates of cholesterol and dolichol synthesis in cell cultures is also functioning in vivo in mouse liver during normal and induced regulatory fluctuations in cholesterol synthesis. Since various tumors exhibit elevated rates of cholesterol synthesis, we will compare dolichol synthesis in tumors and control tissues and relate any differences observed to glycoprotein synthesis. We have previously developed methods to measure the incorporation of radiolabelled acetate and mevalonate into free dolichol and we propose to develop methods to further measure incorporation into dolichyl acyl esters and dolichylphosphoryl mono- and oligosaccharides in order to gain further understanding of the relative fluxes contributing to the pool size of "active dolichol," dolichylphosphate. Preliminary studies have indicated dolichol involvement in differentiation in two systems, developing brain and testes during spermatogenesis. We propose to confirm that an extraordinarily high rate of dolichol synthesis observed in testes is the result of active spermatogenesis and to assign it to a specific differentiating sppermatogenic cell type. We also propose to assign the spike of dolichol synthesis which occurs during the development of mouse brain (preliminary results) to an area of the brain and to a cellular activity, e.g., myelination. Using various differentiating cell cultures we will further determine whether increased dolichol synthesis is associated with the differentiation of cell types other than those in testes and brain. Since these systems all involve cell division as well as differentiation, we will also determine, if possible whether or not alterations in the rate of dolichol synthesis occur during the cell cycle, as we have previously demonstrated for cholesterol synthesis.